chr16-16109488-C-T

Variant names:

• chr16-16109488-C-T
• rs3784867
• NM_004996.4:c.2872-1887C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004996.4(ABCC1):​c.2872-1887C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 152,038 control chromosomes in the GnomAD database, including 5,031 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.25 (5031 hom., cov: 32)
• Consequence: ABCC1 NM_004996.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.212
• Publications: 14 publications found

Genes affected

ABCC1 (HGNC:51): (ATP binding cassette subfamily C member 1 (ABCC1 blood group)) The protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra-and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This full transporter is a member of the MRP subfamily which is involved in multi-drug resistance. This protein functions as a multispecific organic anion transporter, with oxidized glutatione, cysteinyl leukotrienes, and activated aflatoxin B1 as substrates. This protein also transports glucuronides and sulfate conjugates of steroid hormones and bile salts. Alternatively spliced variants of this gene have been described but their full-length nature is unknown. [provided by RefSeq, Apr 2012]

ABCC1 Gene-Disease associations (from GenCC):

• hearing loss, autosomal dominant 77

  Inheritance: AD, Unknown Classification: MODERATE, LIMITED Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae)
• autosomal dominant nonsyndromic hearing loss

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.335 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC1	NM_004996.4	c.2872-1887C>T		intron_variant	Intron 21 of 30	ENST00000399410.8	NP_004987.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC1	ENST00000399410.8	c.2872-1887C>T		intron_variant	Intron 21 of 30	1	NM_004996.4	ENSP00000382342.3

Frequencies

GnomAD3 genomes AF: 0.247 AC: 37475 AN: 151920 Hom.: 5010 Cov.: 32

Gnomad AFR AF: 0.340

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.295

Gnomad ASJ AF: 0.290

Gnomad EAS AF: 0.152

Gnomad SAS AF: 0.304

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.281

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.247 AC: 37533 AN: 152038 Hom.: 5031 Cov.: 32 AF XY: 0.247 AC XY: 18322 AN XY: 74292

African (AFR) AF: 0.340 AC: 14074 AN: 41430

American (AMR) AF: 0.295 AC: 4502 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.290 AC: 1005 AN: 3468

East Asian (EAS) AF: 0.152 AC: 789 AN: 5176

South Asian (SAS) AF: 0.304 AC: 1467 AN: 4820

European-Finnish (FIN) AF: 0.157 AC: 1660 AN: 10578

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.195 AC: 13233 AN: 67988

Other (OTH) AF: 0.288 AC: 608 AN: 2112

Alfa AF: 0.226 Hom.: 10287

Bravo AF: 0.264

Asia WGS AF: 0.277 AC: 960 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.72
DANN	Benign	0.35
PhyloP100		-0.21
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3784867; hg19: chr16-16203345;